Background: Longitudinal estimates of long COVID burden during Omicron remain limited. This study characterized long-term impacts of COVID-19 and booster vaccination on symptoms, Health-Related Quality of Life (HRQoL), and Work Productivity Activity Impairment (WPAI). Methods: Outpatients with ≥1 self-reported symptom and pos. SARS-CoV-2 test at CVS Health United States test sites were recruited between 01/31-04/30/2022. Symptoms, EQ-5D and WPAI were collected via online surveys until 6 mo following infection. Both observed and model-based estimates were analyzed. Effect sizes based on Cohen's d quantified the magnitude of outcome changes over time, within and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for covariates. Logistic regression assessed odds ratio (OR) of long COVID between vaccination groups. Results: At long COVID start (Week 4), 328 participants included 87 (27%) Boosted with BNT162b2, 86 (26%) with a BNT162b2 primary series (Primed), and 155 (47%) Unvaccinated. Mean age was 42.0 years, 73.8% were female, 26.5% had ≥1 comorbidity, 36.9% prior infection, and 39.6% reported ≥3 symptoms (mean: 3.1 symptoms). At Month 6, among 260 participants, Boosted reported a mean of 1.1 symptoms vs. 3.4 and 2.8 in Unvaccinated and Primed, resp. (p<0.001). Boosted had reduced risks of ≥3 symptoms vs. Unvaccinated (observed: OR 0.22, 95% CI, 0.10-0.47, p<0.001; model-based: OR: 0.36, 95% CI, 0.15-0.87, p = 0.019) and Primed (observed: OR 0.29, 95% CI, 0.13-0.67, p = 0.003; model-based: OR 0.59, 95% CI, 0.21-1.65, p = 0.459). Results were consistent using ≥2 symptoms. Regarding HRQoL, among those with long COVID, Boosted had higher EQ-5D Utility Index (UI) than Unvaccinated (observed: 0.922 vs. 0.731, p = 0.014; model-based: 0.910 vs. 0.758, p-value = 0.038) and Primed (0.922 vs. 0.648, p = 0.014; model-based: 0.910 vs. 0.708, p-value = 0.008). Observed and model-based estimates for EQ-VAS and UI among Boosted were comparable with pre-COVID since Month 3. Subjects vaccinated generally reported better WPAI scores. Conclusions: Long COVID neg. impacted HRQoL and WPAI. The BNT162b2 booster could have a beneficial effect in reducing the risk and burden of long COVID. Boosted participants reported fewer and less durable symptoms, which contributed to improve HRQoL and maintain WPAI levels. Limitations included self-reported data and small sample size for WPAI.